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Association of Human Whole-blood NAD+Levels with Nabothian Cyst

Biomedical and Environmental Sciences 2024年第5期37卷 471-478页

作者： XU ling wang Yue Xuan wang Wei FAN Xue CHEN Xue Yu ZHOU Tian yun liU Yu He YU ye YANG Fan JU Zhen Yu ZHOU Yong wang Deng liang Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China NHC Key Lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drugs and DevicesShanghai Institute for Biomedical and Pharmaceutical TechnologiesShanghai 200237China Department of Applied Statistics Johannes Kepler University LinzLinz 4040Austria Hematology Center Beijing Key Laboratory of Pediatric Hematology OncologyNational Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in ChildrenMinistry of EducationBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Biostatistics School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012ShandongChina Clinical Medicine School of Basic MedicineShanghai Medical College Fudan UniversityShanghai 200032China Department of Biochemistry and Molecular Biology Hengyang Medical SchoolUniversity of South ChinaHengyang 421001HunanChina Administrative Office Total Quality Management OfficeTotal Quality Management InstituteShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China The first affiliated {2. of jinan {4. Institute of Aging and Regenerative MedicineJinan UniversityJinan 510632GuangzhouChina Department of Scientific Research The First Affiliated Hospital of Huzhou UniversityHuzhou 313000ZhejiangChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated HospitalFujian Medical UniversityFuzhou 350209FujianChina Fujian Provincial Institutes of Brain Disorders and Brain Sciences The First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Fujian Provincial Clinical Research Center for Neurological

Objective little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian *** study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese *** Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian *** The mean age was 4..0±11.5 {2.ars,and the mean level of NAD^(+)was 31.3±5.3μmol/*** cysts occurred in 184.2..7%)participants,with single and multiple cysts in 100(15.0%)and84.12.6%)participants,*** total nabothian cyst prevalence gradually decreased from37.4.to 2..6%from Q1 to Q4.of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)*** compared with the highest NAD^(+)quartile(≥34.4.mol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14.3.14.for total nabothian *** risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 2..0 to35.0μmol/***:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.

关键词： Nicotinamide adenine dinucleotide Nabothian cyst Female Risk factor

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A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 466-472页

作者： Zhi-Bo lin Chun-yun Feng {2.n li An-Peng {4. Hai-Sen Sun A-Yong Yu Shi-hao Chen National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Department of Ophthalmology the Quzhou Affiliated Hospital of Wenzhou Medical UniversityQuzhou People’s HospitalQuzhou 324000Zhejiang ProvinceChina

●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were *** family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.62.C>T(***2.8Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical *** result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.

关键词： PAX6 gene atypical aniridia missense mutation mutation

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Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex

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Neural Regeneration Research 2024年第8期19卷 1781-1788页

作者： Zongqin Xiang Shu He Rongjie Chen Shanggong {2.u Minhui {2.u {2.ang Xu jiajun Zheng Zhouquan jiang long Ma Ying Sun Yongpeng qin Yi Chen Wen {2. Xiangyu wang Gong Chen Wen{2.ang Lei Guangdong-Hong Kong-Macao Institute of CNS Regeneration(GHMICR) Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Neurosurgery The First Affiliated HospitalJinan UniversityGuangzhouGuangdong ProvinceChina Laboratory for Neuroimmunology in Health and Diseases Guangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouGuangdong ProvinceChina VIB-KU Leuven Center for Brain&Disease Research LeuvenFlemish RegionBelgium

Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous *** r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain *** addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing *** this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse ***-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local *** addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable ***,two-photon Ca2.imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural *** conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.

关键词： astrocyte-to-neuron conversion Ca2.imaging direct lineage conversion glia astrocyte in vivo reprogramming lineage-tracing mice NeuroD1 neuron two-photon imaging

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Decreased AKAP4.PKA signaling pathway in high DFI sperm affects sperm capacitation

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Asian Journal of Andrology 2024年第1期26卷 25-33页

作者： Kun Zhang Xiu-Hua Xu jian Wu Ning wang Gang {2. Gui-Min hao jin-Feng Cao Hebei Key Laboratory of Infertility and Genetics Department of Reproductive MedicineSecond Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Reproductive Medicine Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000China Department of Neurology The 980th Hospital of the People's Liberation Army Joint Logistics Support Force(Bethune International Peace Hospital)Shijiazhuang 050000China.

The sperm DNA fragmentation index(DFI)is a metric used to assess DNA fragmentation within *** in vitro fertilizationembryo transfer(IVF-ET),high sperm DFI can lead to a low fertilization rate,poor embryo development,early miscarriage,etc.A kinase anchoring protein(AKAP)is a scaffold protein that can bind protein kinase A(PKA)to subcellular sites of specific substrates and protects the biophosphorylation *** protein antigen 17(SPA17)can also bind to *** study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI(H-DFI)patients during *** addition,the study investigates the expression of AKAP,protein kinase A regulatory subunit(PKARIl),and SPA17 between H-DFI and low sperm DFI(L-DFI)***17 at the transcriptional level is abnormal,the translational level increases in H-DFI patients,and the expression of AKAP4.PKARIl protein decreases.H,O,has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm *** indicates that H,O,increases the expression of sperm SPA17 protein and suppresses AKAP4.PKARIl protein *** processes inhibit sperm capacitation and reduce acrosomal *** culture data and IVF outcomes have been *** H-DFI group has a lower fertilization ***,the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4.PKARIl proteins,blocked sperm capacitation,and reduced occurrence of acrosome reaction.

关键词： AKAP PKA SPA17 sperm capacitation sperm DNA fragmentation index

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Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

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Journal of Wuhan university of Technology(Materials Science) 2024年第3期39卷 682-688页

作者：吴治文 wang Zihao {2. Zepeng QU liting 于涛 College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan 517000China

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different *** this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis *** the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of *** the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this *** the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the *** dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 2..8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement *** work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.

关键词： bone repair self-reinforce chemoresponsive hydrogen bond

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Saponin Ⅰ from Shuitianqi(Rhizoma Schizocapasae Plantagineae) inhibits metastasis by negatively regulating the transforming growth factor-β1/Smad7 network and epithelial-mesenchymal transition in the intrahepatic metastasis Bagg's Albino/c mouse model

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Journal of Traditional Chinese Medicine 2024年第4期44卷 642-651页

作者： LYU Meixian ZHOU Huan ZHI limin ZHOU jinling GAN Rizhi qin Yanping HE Nengting ZUO Qiqi li hao DONG Min liANG Gang Pharmaceutical College Guangxi Medical UniversityNanning 530022China Department of Pharmacy Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530022China Drug clinical trial Facility office the People's Hospital of Guangxi Zhuang Autonomous RegionNanning 530022China College of Pharmacy Guangxi University of Chinese MedicineNanning 530022China Department of Pharmacy the Second Affiliated Hospital of Guangxi Medical UniversityNanning 530005China Department of Pharmacy People's Hospital of Guangxi HezhouHezhou 542899China Department of Pharmacy Guangzhou Women and Children's Medical Center Liuzhou HospitalLiuzhou 545000China Department of Pharmacy First Affiliated Hospital of Gannan Medical UniversityGannan 341000China

OBJECTIVE:To examine the influence of SaponinⅠfrom Shuitianqi(Rhizoma Schizocapasae Plantagineae)(SSPHⅠ)on hepatocellular carcinoma(HCC)metastasis,and to elucidate the underlying ***:The intrahepatic metastasis Bagg's Albino/c(BALB/c)mouse model was established with human hepatocellular carcinomas(HepG2.cells,then treated with normal saline(once per day),cisplatin(2.mg/kg,once every 2.d),and SSPHⅠ(2.,50,and 75 mg/kg,once per day).Then,we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology ***:Based on our analysis,SSPHⅠsignificantly alleviated hepatocyte necrosis and tumor cells ***,SSPHⅠsuppressed extracellular matrix(ECM)degradation and angiogenesis via a decrease in matrix etalloproteinase-2.MMP-2.,MMP-9,CD31,CD3{2.and vascular endothelial growth factor(VEGF)***,SSPHⅠrepressed invasion and metastasis by suppressing the transforming growth factor-β1(TGF-β1)/Smad7 axis and epithelial-mesenchymal transition(EMT),as evidenced by the scarce TGF-β1,Ncadherin,and Vimentin expressions,and elevated Smad7 and E-cadherin ***:The SSPHⅠ-mediated negative regulation of the TGF-β1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

关键词： carcinoma,hepatocellular epithelial-mesenchymal transition transforming growth factor beta1 Smad7 protein Saponin I from Shuitianqi(Rhizoma Schizocapasae Plantagineae)

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Delayed diagnosis in inflammatory bowel disease:Time to consider solutions

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World Journal of Gastroenterology 2024年第35期30卷 3954-3958页

作者： hao Lv hao-Yu {2. hao-Nan Zhang Yang {2.u Department of General Surgery Xi'an Jiaotong University Second Affiliated HospitalXi'an 710004Shaanxi ProvinceChina

In this editorial,we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology,with a specific focus on the delayed diagnosis of inflammatory bowel disease(IBD).IBD,which includes Crohn's disease and ulcerative colitis,is a chronic intestinal disorder.A time lag may exist between the onset of inflammation and the appearance of signs and symptoms,potentially leading to an incorrect or delayed diagnosis,a situation referred to as the delayed diagnosis of *** diagnosis is crucial for effective patient treatment and prognosis,yet delayed diagnosis remains *** reasons for delayed diagnosis of IBD are numerous and not yet fully *** key factor is the nonspecific nature of IBD symptoms,which can easily be mistaken for other ***,the lack of specific diagnostic methods for IBD contributes to these *** diagnosis of IBD can result in numerous adverse consequences,including increased intestinal damage,fibrosis,a higher risk of colorectal cancer,and a decrease in the quality of life of the ***,it is essential to diagnose IBD promptly by raising physician awareness,enhancing patient education,and developing new diagnostic methods.

关键词： Inflammatory bowel disease Delayed diagnosis Diagnostic methods Early diagnosis Consequences of inflammatory bowel disease

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Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in {2.

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World Journal of Gastroenterology 2024年第9期30卷 1108-1120页

作者： Ying-yun Yang Ke-Min li Gui-Fang Xu Cheng-Dang {2. Hua Xiong Xiao-Zhong {2. Chun-Hui {2. Bing-Yong Zhang Hai-Xing jiang jing Sun Yan Xu li-Juan Zhang hao-Xuan Zheng Xiang-Bin Xing liang-jing {2. Xiu-li Zuo Shi-Gang Ding Rong lin Chun-Xiao Chen Xing-Wei {2. jing-Nan li Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China Department of Gastroenterology Nanjing Drum Tower HospitalNanjing 21000Jiangsu ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Gastroenterology Renji HospitalShanghai 200127China Department of Gastroenterology Union Hospital of Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina Department of Gastroenterology West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Gastroenterology and Hepatology The People’s Hospital of Zhengzhou UniversityThe Henan Provincial People’s HospitalZhengzhou 450003Henan ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Ruijin hospital Shanghai jiaotong university School of Medicine Shanghai Jiao Tong UnivesrityRuijin HospitalSchool MedicineShanghai 200025China Department of Gastroenterology and Hepatology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Gastroenterology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Department of Gastroenterology Nanfang HospitalGuangzhou 510080Guangdong ProvinceChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina Department of Gastroenterology The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Gastroenterology Shandong University Qilu HospitalJinan 250012Shandong ProvinceChina Department of Gastroenterology Peking University Third HospitalBeijing 100191China Department of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022Hubei Pr

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully *** lack of consensus regarding its treatment has resulted in varied treatment *** To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in *** We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and *** and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after {2.wk of *** Three thousand five hundred sixty-three patients from {2. centers across 2.2.cities in china were *** pain(68.0%),abdominal distension(62.6%),and postprandial fullness({2..5%)were the most common presenting *** was classified as chronic non-atrophic in 69.9%of *** those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat *** patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more *** those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more *** CEG is a multifactorial disease which is common in Asian patients and has non-specific *** may play a major role in its detection and *** should be individualized based on symptom profile.

关键词： Chronic erosive gastritis Symptom Endoscopic findings Treatment pattern Real-world

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Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

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Frontiers of Medicine 2024年第2期18卷 303-314页

作者： Yi Ding Xiaoli Xu Zhuojun Xin Qiuyu Cao jiaojiao Huang Xianglin Wu Yanan Huo {4. Wan Yingfen {4. Ruying Hu lixin Shi {4.g Su Xuefeng Yu li Yan Guijun {4. Xulei Tang Gang Chen Min Xu Tiange wang Zhiyun Z{12. Zhengnan Gao Guixia wang Feixia Shen Zuojie Luo li Chen Qiang li Zhen ye Yinfei Zhang C{12. liu Youmin wang Tao Yang Huacong Deng Lulu Chen Tianshu Zeng jiajun Z{12. Yiming Mu Shengli Wu Yuhong Chen jieli Lu Wei{4.g wang Guang Ning Yu Xu Yufang Bi Mian li Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China jiangxi Provincial People’s hospital Affiliated to Nanchang UniversityNanchang330000China Department of Endocrinology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou310000China Department of Endocrinology Affiliated Hospital of Guiyang Medical UniversityGuiyang550000China Xinhua hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200000China Tongji hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China Sun Yat-sen Memorial hospital Sun Yat-sen UniversityGuangzhou510000China Department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Department of Endocrinology The First Hospital of Lanzhou UniversityLanzhou730000China Fujian Provincial hospital Fujian Medical UniversityFuzhou350000China Dalian Municipal Central hospital Affiliated of Dalian Medical UniversityDalian116000China Department of Endocrinology The First Hospital of Jilin UniversityChangchun130000China Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Qilu hospital of Shandong university Jinan250000China Department of Endocrinology The Second Affiliated Hospital of Harbin Medical UniversityHarbin150000China Department of Endocrinology Cen

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with *** included 104.38 partici{2.ts from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A longitudinal Study,with self-reported time of daily-life *** isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD ***-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working *** stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long *** pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active *** U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical *** divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词： sleep physical activity chronic kidney disease isotemporal substitution behavioral pattern

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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2.positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： jialin Zhang Gengshen Yin Chunmiao {2. Man Feng Changhua ji Wenzhong Zhou Fei {4. lixiang Yu Shuya Huang Zhigang Yu Department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China Department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2.HER2.-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2. breast cancer. However, the efficacy of pyrotinib in HER2. breast cancer with primary trastuzumab resistance is ***: HER2. breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2.downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2. breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2.downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2.downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2. breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2. breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2.downstream pathways in HER2. breast cancer with primary resistance

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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